Mathieu van der Poel completed a Netherlands double in Strade Bianche after Chantal van den Broek-Blaak had earlier won the women’s race in Siena.
Van der Poel, 26, punched clear on the final climb to win by five seconds from world champion Julian Alaphilippe.
Ex-Tour de France winner Egan Bernal was third with Ineos Grenadiers team-mate, Britain’s Thomas Pidcock, fifth.
Van den Broek-Blaak, 31, won by seven seconds from Elisa Longo Borghini.
In the men’s race Pidcock, 21, was the first British rider home, 54 seconds behind the winner, with Simon Carr 11th and Owain Doull 30th.
After securing victory on the famous white dirt roads of Tuscany, Van der Poel said: “Strade is one of the races I really wanted to win, and it’s really cool to win it today.
“I felt pretty good, I launched an attack on the last gravel section and I came with Bernal and Alaphilippe in the lead.
“We did a pretty strong ride the three of us. I felt I had something left in the legs to go all out on the last climb, and it’s amazing to finish it off in this way.”
Van den Broek-Blaak is the fourth successive Dutch winner of the women’s event, following Anna van der Breggen (2018) and Annemiek van Vleuten in 2019 and 2020.
Lizzy Banks was the top Briton in 48th place, six minutes 27 seconds back in the 136km run.
Van Vleuten was denied a third consecutive win, finishing 11 seconds behind Van den Broek-Blaak in fourth.
Van den Broek-Blaak said afterwards: “My win is due to team work. I had the instruction from the team to not ride at the front.
“I didn’t think I’d drop Elisa Longo Borghini in the final climb but I did. This is a very big day in my cycling career.”
Men’s result:
1. Mathieu van der Poel (Ned/Alpecin-Fenix) 4hrs 40mins 29secs
2. Julian Alaphilippe (Fra/Deceuninck/Quick Step) +5secs
3. Egan Bernal (Col/Ineos Grenadiers) +20secs
4. Wout van Aert (Bel/Team Jumbo-Visma) +5secs
5. Thomas Pidcock (GB/Ineos Grenadiers) + 54secs
6. Michael Gogl (Aut/Team Qhubeka ASSOS) same time
7. Tadej Pogacar (Svk/UAE-Team Emirates)
8. Simon Clarke (Aus/Team Qhubeka ASSOS) + 2mins 25secs
9. Jakob Fuglsang (Den/Astana-Premier Tech) same time
10. Pello Bilbao (Spa/Bahrain-Victorious) + 2mins 39secs
Women’s result:
1. Chantal van den Broek-Blaak (Ned/Team SD Worx) 3hrs 54mins 40secs
2. Elisa Longo Borghini (Ita/Trek-Segafredo) + 7secs
3. Anna van der Breggen (Ned/Team SD Worx) +9secs
4. Annemiek van Vleuten (Ned/Movistar Team Women) +11secs
5. Cecilie Uttrup Ludwig (Den/FDJ Nouvelle-Aquitaine Futuroscope) same time
6. Demi Vollering (Ned/Team SD Worx)
7. Marianne Vos (Ned/Jumbo-Visma Women Team) +23secs
8. Marta Cavalli (Ita/FDJ Nouvelle-Aquitaine Futuroscope) +27secs
9. Katarzyna Niewiadoma (Pol/Canyon-SRAM Racing) +30secs
10. Ellen van Dijk (Ned/Trek-Segafredo) +32secs